Nutrition and the Gastroenterologist – Putting Science into PracticeSheila E. Crowe, MD, FRCPC, FACP, FACG, AGAF

Division of GastroenterologyUniversity of California, San Diego

What to Eat and What Not to Eat?

• Nearly every patient who sees a GI practitioner wants to know is it something they eat and/or is it something they are missing from their diet that is the cause of their GI and other health problems

• The popularity of many types of diets underscore the notion that what we eat is the key to health and wellbeing

• Marketing of food promoting potential health benefits is becoming more common

Food and the Digestive Tract: Friend or Foe?

• The average human ingests a large amount of food in their lifetime – ~ 60,000 pounds ‐ 27,273 kilograms ‐ 30 tons

• The vast majority benefit from this ingestion but a small percentage develop complications: – Food poisoning– Food allergies– Food sensitivities

• There is a reported increase in food allergies, celiac disease and seemingly of food sensitivities too

Brandtzaeg, Nat Rev Gastroenterol Hepatol, 7: 380-400, 2010

Biological Variables that Influence the Developing Immunophenotype of an Infant

Classification of Adverse Reactions to Food

Adapted from Boyce JA et al. JACI.2010;126(6):1105

GI Disorders and ARF

• GI food allergy• Food protein enteropathies (milk, soy)• Celiac disease• Eosinophilic gastroenteritis, esophagitis• Lactose and other carbohydrate intolerance• Irritable bowel syndrome• Inflammatory bowel disease• Dyspepsia, GERD, peptic ulcer

Forms of Non-Immune Adverse Reactions to Food

• Food toxicity or food poisoning (SEB toxin, microbes)• Anaphylactoid or pseudo‐allergic (strawberries, etc)• Pharmacologic (sulfites, tyramine)• Metabolic (lactose intolerance)• Mechanical (in the setting of altered anatomy/function)• Idiosyncratic • Psychological (conditioned)

Immunological Reactions to Food

• Food hypersensitivity (IgE‐mediated)• Celiac disease (T‐call mediated) • Food protein enteropathies (mixed)

• Hypersensitivity• Immune complexes• T‐cells 

Food Allergy: Epidemiology4‐5%

20‐30%

30‐40%

50%

70%

of the population have food allergy

of the population think they have food allergy

of patients with FA have asthma/atopic dermatitis

of anaphylaxis treated in ED are due to FA

of patients with FA have + FHx of atopic diseases

Branum AM et al. Pediatrics, 124(6): 1549, 2009Sicherer SH, Sampson HA, JACI, 125:S116-25, 2010

Food Allergy – Key Information

Boyce JA et al, JACI, 126(6):1105, 2010 Santos A et al, Pediatr Allergy Immunol; 21(8):1127, 2010

Boyano-Martínez T et al, JACI, 110(2):304, 2002

• Adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food

Definition

• Egg:       >50% by age 5•Milk:       >80% by age 5• Peanut:  ~20%

Outgrowing phenomena

•Milk, soy, eggs, wheat, peanuts, tree nuts, fish and shellfishBig 8

Food Allergy & Anaphylaxis: Wheat• 4‐8% of children, 2‐4% adults have food allergies• 65% of children lose reactivity to wheat by age 12• GI symptoms in food allergy (in 30‐70%):

– Edema of oropharyngeal mucosa– Nausea/vomiting, diarrhea, abdominal pain, bloating

• Dermatological: Urticaria, eczema• Respiratory Tract: Asthma, rhinitis, otitis• Systemic:  Anaphylaxis

– Wheat‐dependent exercise‐induced anaphylaxis (WDEIA)– IgE to omega‐5‐gliadin  

Keet, CA et al,Ann Allergy Asthma Immunol, 102:410; 2009Inomata N, Curr Opin Allergy Clin Immunol, 9:238; 2009

Oral Allergy Syndrome Localized IgE  ‐ Initial sensitization to pollens results in IgE that cross reacts 

with fruit and vegetables Raw fruit and vegetables

– Birch pollen – apple, peach, pear, almond, hazelnut, potato, carrot– Ragweed pollen – melons, banana, gourd family– Mugwort pollen – celery, carrot, spices– Grass pollen ‐ tomato

Itching, ± swelling and/or tingling Confined to lips, tongue, roof of mouth and throat Affects patients with pollen allergy

Hofmann A, et al. Curr Allergy Asthma Rep, 8(5):413, 2008

Latex – Food Allergy Syndrome

• Sensitization to latex results in IgE that cross reacts with fruit and vegetables

• Exposure to foods give same symptoms as latex

• Natural Rubber Latex contains over 200 proteins, 10 bind IgE (HEV b 1‐10)

• Food associations:– Kiwi (5)– Potato, tomato (7)– Avocado, chestnut, banana (6)

Other Immune-Mediated Food Allergy

What is Gluten Sensitivity?

Ludvigsson, J et al, Gut, 62(1):43-52; 2013

Oslo DefinitionsGluten Sensitivity Due to Celiac Disease (CD)

A chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals

Non-Celiac Gluten Sensitivity (NCGS)

One or more immunological, morphological and/or symptomatic alterations triggered by gluten ingestion in individuals in whom celiac disease has been excluded

Changing Prevalence of Celiac Disease• Prevalence of up to ~1:100 in most genetically susceptible populations, 0.71% in NHANES study

• Less than 10‐15% of current cases of CD have been diagnosed in the US

• CD is 4 to 4.5 times more prevalent than 50 yrs ago

• Cause of “CD epidemic” unknown – Dietary – grains with increased gluten, increased wheat in diets worldwide

– Other environmental – Microbiota

Fasano et al, Arch Int Med, 163:286, 2003Rubio-Tapa et al, Gastroenterology, 137: 88, 2009

AGA Technical Review, Gastroenterology, 131:1981, 2006Virta et al, Scand J Gatroenterol, 44:933, 2009

Rubio-Tapia, Am J Gastroenterol, 2012

Between Celiac Disease & IBS:The “No Man’s Land” of Gluten Sensitivity

Dietary Treatments for IBS and Other Functional GI Disorders

Diet Evidence for useLow fat LimitedGluten-free LimitedSpecific carbohydrate intolerance Little to noneLow FODMAP LimitedPaleolithic MinimalCandida NoneHypoallergenic Little to none

Controlled Trial of GF Diet in IBS-D• RCT in 45 subjects with IBS-D comparing 4 wks of

GFD versus GCD• Stratified by HLA DQ 2/8 status • Assessed BMs, gut transit, permeability, histology• More BMs in GCD, especially if HLADQ2/8+• GCD increased SB permeability, > in HLA DQ2/8+• GFD benefitted IBS-D patients (stool frequency,

permeability) especially if HLA DQ2/8 positive1

• No effect on transit or histology

Vasquez-Roque, et al, Gastroenterol, 144:903, 2013

Gluten Containing Diet has Greater Effects in IBS-D with HLA DQ2/8 Genes

Vasquez-Roque, et al, Gastroenterol, 144:903, 2013

Adverse Reactions to FODMAPs

Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols• Fructose and fructans• Sorbitol• Sucrose• Lactose

Many foods (grains including wheat starch, fruits, vegetables) contain FODMAPs

Gluten Causes Symptoms in IBS Patients Without Celiac Disease

No Effect of Gluten after Reduced FODMAP Diet in IBS Patients

• 37 subjects with IBS (Rome III) reporting NCGS (celiac disease meticulously excluded) underwent double-blind cross-over study

• 2 wks low FODMAP diet resulted in significant improvement of GI symptoms and fatigue

• Challenge with gluten (high, low or control) did not result in symptomatic or biological changes

• Suggests sensitivity may not be due to gluten

J. Biesiekierski, et al, Gastroenterol, 145:320, 2013

No Effect of Gluten after Reduced FODMAP Diet in IBS Patients

J. Biesiekierski, et al, Gastroenterol, 145:320, 2013

Gluten Coexists with Nonabsorbed Fructans and Other Saccharides

Proposed Mechanisms of Non-Celiac Gluten or Wheat Sensitivity

Wheat ingestion

Immune Activation/Low grade

inflammation

Excess Fructans

Microbiome changes

AlteredPermeability

Gas production & SCFA formation

Poorly AbsorbedCarbohydrates

Fermentation

GI SymptomsAdapted from Eswaran S, et al. Gastroenterol Hepatol 2013;9:85. Vazquez-Roque MI, et al. Gastroenterology 2013;144:903

Gluten-mediated

NoceboEffect

SCFA = short chain fatty acids

Testing for Adverse Reactions to Food 

• Food allergy or hypersensitivity:– IgE – skin prick, RAST– Histology – Celiac disease serology– HLA DQ2/8– CBC, differential– Skin patch testing– Histamine release studies– Leukotriene release studies– Other tests 

• Food sensitivities or intolerances (non‐immune):– Lactose breath test– Fructose breath test– Digestive enzyme assays

• No evidence for many tests– IgG antibodies to foods – Food cytotoxicity assays (Alcat)– Tests of barrier function– Many others but not based on 

science or EBM

Leung & Crowe, Food intolerance and food allergy. In: The Gastrointestinal Nutrition Desk Reference, 2011

Take Home Points• Food intolerances and allergies appear to be increasing • Lactose intolerance is common and easily treated• Celiac disease is common and easily screened for• Food allergies are not rare and can be identified with subsequent 

dietary elimination providing benefit• Patients can have a specific ARF and also have other GI conditions• The role of gluten, FODMAPs, and other foods in IBS/FGIDs 

remains unclear. However, identifying specific food intolerances can be beneficial for IBS patients

• The microbiome/SIBO also contribute to food intolerances• Patients appreciate the assessment even if it turns out to be 

negative and they have the non‐specific food sensitivity common to most IBS patients 

DeGaetani & Crowe, CGH, 8: 755, 2010